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MA 06 - Lung Cancer Biology I (ID 660)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
MA 06.12 - Genomic Rearrangements of Lung Adenocarcinomas with Fusion Driver Gene (ID 9133)
15:45 - 17:30 | Author(s): Y.T. Kim
A subset of lung adenocarcinoma is transformed by fusion genes, i..e. EML4-ALK, KIF5B-RET. Practically, fusion genes are detected using PCR, FISH and/or RNAseq. Although TCGA project sequenced many lung cancer genomes, little is known about the genomic landscape of driver-fusion positive lung adenocarcinoma. In particular, we wondered the frequency and impact of complex genomic rearrangements, such as chromothripsis, chromoplexy, and chromoanasynthesis, in the pathogenesis of lung adenocarcinomas.
We performed whole-genome sequencing analyses for 38 pairs of driver-fusion-positive lung adenocarcinoma and its normal counterpart samples. These 38 tumors harbored one driver fusion genes such as EML4-ALK, KIF5B-RET, and CD74-ROS1. We mapped reads using Burrows-Wheeler Aligner, and processed aligned reads with Picard and Genome Analysis Toolkit. We analyzed tumor purity, ploidy and copy number variations using Sequenza. We called point mutations and indels using Mutect and Strelka. And we also called structural variations using Delly.
The number of somatic point mutations of these samples was lower than general lung adenocarcinomas. Mutational signature analysis revealed that signature 1 and 5 are major factors in these samples. More than 70% of driver fusion genes were established by complex genomic rearrangements rather than simple events. Based on the copy number change and the microhomology, replication-based mechanism is presumed to be a main cause of these complex events. Somatic mutation on TP53 was rare in these samples.
Much of driver fusion genes in lung adenocarcinomas are made by complex genomic rearrangements. TP53-independent replication-based mechanism is critical to these phenomena.
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